To stick or not to stick: the new leukocyte homing paradigm.

The immune system is formed by leukocytes. They are passively transported through the body by the vascular system, but their entrance into tissues requires a coordinated series of events, namely activation of leukocyte integrins, adhesion to the vascular endothelium, and migration. There are four steps in this process, which begin with the rolling of leukocytes along the vascular endothelium, followed by signaling which activates leukocyte integrins, thus leading to tight adhesion to the endothelium and finally transmigration. Substantial progress has been made recently in elucidating the molecular events that induce rolling and signaling, partly as a result of the study of double-knockout mice that are deficient for genes encoding two selectins.